Inherited Epidermolysis Bullosa
Conditions
Keywords
Epidermolysis bullosa, Wound healing, Epithelialization
Brief summary
The purpose of this study was to compare intra-individually the reepithelialization of skin lesion(s) in inherited Epidermolysis bullosa (either 1 wound ≥10 cm2 and ≤200 cm2 in size divided in 2 equal halves or 2 comparable wounds of ≥5 cm2 each) treated with Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only.
Detailed description
This study was designed as an open-label, prospective, controlled, blindly evaluated, monocentric phase II case series documentation in patients with inherited Epidermolysis bullosa (EB). The investigator either identified 1 EB wound ≥10 cm2 and ≤200 cm2 in size and divided it into 2 halves or selected 2 comparable wounds of ≥5 cm2 each. One (half of the) EB wound was treated with Oleogel-S10 and non-adhesive wound dressing. The other wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as control. Wound dressings were changed about every 24 to 48 hours until discharge from hospital or until the end of treatment at Day 14 in 'recent wounds' or Day 28 in 'chronic wounds'. This was an open-label study. The investigator, the participant, and the sponsor knew the identity of the treatment. Two independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound (half) that were taken before start of treatment, during wound dressing changes and at the end of treatment on Day 14/Day 28.
Interventions
DRUGOleogel-S10
1 cm or 125 µL or 115 mg Oleogel-S10 per cm2 wound area (corresponds to thickness of approximately 1 mm or 0.04 inch) every 24 to 48 hours until discharge from hospital or until the end of treatment at Day 14 in 'recent wounds' or Day 28 in 'chronic wounds'.
DEVICEMepilex® soft silicone faced polyurethane foam dressing
Mepilex® soft silicone faced polyurethane foam dressing was changed about every 24 to 48 hours until discharge from hospital or until the end of treatment at Day 14 in 'recent wounds' or Day 28 in 'chronic wounds'.
Sponsors
Birken AG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blinded comparison of wound photo series by two independent experts
Eligibility
Sex/Gender
ALL
Age
1 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged 1-95 years 2. Patient and/or his/her legal representative was informed, read and understood the patient information/informed consent form and gave written informed consent 3. Patients with inherited EB with at least 1 skin lesion between 10 cm2 and 200 cm2 (alternatively 2 comparable lesions of at least 5 cm2 each) 4. Patient and/or his/her legal representative was able and willing to follow study procedures and instructions including the following: 1. Application of Oleogel-S10 on (1 half of) the wound at every wound dressing change 2. Regular visits during the treatment period (14 days in 'recent wounds' to 28 days in 'chronic wounds') 5. Negative pregnancy test in women of childbearing potential within 7 days before start of treatment 6. Women of childbearing potential agreed to use an effective method of contraception (Pearl Index \< 1, e.g. hormonal contraception including the combined oral contraceptive pill, the transdermal patch, and the contraceptive vaginal ring, intrauterine devices or sterilization) during treatment and for at least 6 months thereafter 7. Men of procreative capacity agreed to use an effective method of contraception during treatment and for at least 6 months thereafter
Exclusion criteria
1. Systemic treatment with steroids during the last 30 days 2. Uncontrolled diabetes mellitus or diabetic ulcers 3. Diseases or conditions that could, in the opinion of the investigator, interfere with the assessment of safety, tolerance or efficacy 4. Skin disorders adversely affecting wound healing or involving the areas eligible for study treatment 5. Hypersensitivity to the trial medication or surgical dressings to be used 6. Multiple allergic disorders 7. Administration of investigational drugs within 3 months before screening 8. Investigations or changes in management for an existing medical condition 9. Low probability to complete the study per protocol for whatever reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intra-individual Difference in Reepithelialization of Wound (Halves) at Day 14 in 'Recent Wounds' or Day 28 in 'Chronic Wounds' | 14 days for 'recent wounds', 28 days for 'chronic wounds' | The primary end point was the progress of reepithelialization from baseline to either Day 14 ('recent wounds') or Day 28 ('chronic wounds') of the EB wound (half) treated with Oleogel-S10 and non-adhesive wound dressing (Mepilex®) intra-individually compared to the other wound (half) covered with non-adhesive wound dressing only (intra-individual comparison). Two independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound (half) that were taken before start of treatment, during wound dressing changes and at the end of treatment on Day 14/Day 28. They evaluated each series and decided whether 1 wound (half) reepithelialized faster than the other ('winner'), or whether there was no difference in reepithelialization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Wound Epithelialization at Day 7±1 | Day 7±1 | The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 7±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg. |
| Percentage of Wound Epithelialization at Day 14±1 | Day 14±1 | The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 14±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg. |
Countries
Germany
Participant flow
Recruitment details
Participants were enrolled from 03 Nov 2010 to 14 Jun 2011 at 1 center (University Medical Center Freiburg) in 1 country (Germany).
Pre-assignment details
12 wounds in 10 participants (2 cycles of treatment in 2 participants) were treated with study medication. The reepithelialization was compared intra-individually in either 2 halves of an Epidermolysis bullosa (EB) wound ≥10 cm2 and ≤200 cm2 in size or in 2 EB wounds ≥5 cm2 in size, i.e. the total number of participants was 10 in the overall study.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants One (half of an) EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with Oleogel-S10 and non-adhesive wound dressing. The other wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as control. | 10 |
| All Study Participants One (half of an) EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with Oleogel-S10 and non-adhesive wound dressing. The other wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as control. | 12 |
| Total | 22 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 5 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 20 years |
| Region of Enrollment Germany | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Intra-individual Difference in Reepithelialization of Wound (Halves) at Day 14 in 'Recent Wounds' or Day 28 in 'Chronic Wounds'
The primary end point was the progress of reepithelialization from baseline to either Day 14 ('recent wounds') or Day 28 ('chronic wounds') of the EB wound (half) treated with Oleogel-S10 and non-adhesive wound dressing (Mepilex®) intra-individually compared to the other wound (half) covered with non-adhesive wound dressing only (intra-individual comparison). Two independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound (half) that were taken before start of treatment, during wound dressing changes and at the end of treatment on Day 14/Day 28. They evaluated each series and decided whether 1 wound (half) reepithelialized faster than the other ('winner'), or whether there was no difference in reepithelialization.
Time frame: 14 days for 'recent wounds', 28 days for 'chronic wounds'
Population: 12 wounds in 10 participants (intra-individual comparison, 2 cycles of treatment in 2 participants) were evaluated by assessors that were blind to treatment. 'Undecided' wounds that were either evaluated controversially (n=2) or as being equal (n=2) were excluded from the analysis of the primary efficacy variable.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| All Study Participants | Intra-individual Difference in Reepithelialization of Wound (Halves) at Day 14 in 'Recent Wounds' or Day 28 in 'Chronic Wounds' | Faster healing of wound treated with Oleogel-S10 | 8 Wounds |
| All Study Participants | Intra-individual Difference in Reepithelialization of Wound (Halves) at Day 14 in 'Recent Wounds' or Day 28 in 'Chronic Wounds' | Faster healing of wound treated with dressing | 0 Wounds |
Comparison: The intra-individual difference in reepithelialization of wound (halves) was tested using a two-sided exact binomial test. The test was performed at a significance level of 5% for the null-hypothesis of no difference δ = 0 against the hypotheses δ ≠ 0: H0: δ = 0 H1: δ ≠ 0p-value: =0.008Two-sided exact binomial test
Secondary
Percentage of Wound Epithelialization at Day 14±1
The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 14±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg.
Time frame: Day 14±1
Population: As 2 participants received 2 cycles of treatment each, 12 wounds were treated with study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Study Participants | Percentage of Wound Epithelialization at Day 14±1 | 87.7 Percentage of wound epithelialization |
| Non-adhesive Wound Dressing Only | Percentage of Wound Epithelialization at Day 14±1 | 79.2 Percentage of wound epithelialization |
Comparison: The intra-individual difference in median percentage of wound epithelialization was tested using a two-sided Wilcoxon test.p-value: 0.33Wilcoxon (Mann-Whitney)
Secondary
Percentage of Wound Epithelialization at Day 7±1
The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 7±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg.
Time frame: Day 7±1
Population: As 2 participants received 2 cycles of treatment each, 12 wounds were treated with study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Study Participants | Percentage of Wound Epithelialization at Day 7±1 | 69.7 Percentage of wound epithelialization |
| Non-adhesive Wound Dressing Only | Percentage of Wound Epithelialization at Day 7±1 | 57.4 Percentage of wound epithelialization |
Comparison: The intra-individual difference in median percentage of wound epithelialization was tested using a two-sided Wilcoxon test.p-value: =0.21Wilcoxon (Mann-Whitney)